A Systems-Based Analysis of Mono- and Combination Therapy for Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections.

Antimicrobial resistance is a global threat. As "proof-of-concept," we employed a system-based approach to identify patient, bacterial, and drug variables contributing to mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKp) bloodstream infections exposed to colistin (COL) and ceftazidime-avibactam (CAZ/AVI) as mono- or combination therapies. Patients (n = 49) and CRKp isolates (n = 22) were part of the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-1), a multicenter, observational, prospective study of patients with carbapenem-resistant Enterobacterales (CRE) conducted between 2011 and 2016. Pharmacodynamic activity of mono- and combination drug concentrations was evaluated over 24 h using in vitro static time-kill assays. Bacterial growth and killing dynamics were estimated with a mechanism-based model. Random Forest was used to rank variables important for predicting 30-day mortality. Isolates exposed to COL+CAZ/AVI had enhanced early bacterial killing compared to CAZ/AVI alone and fewer incidences of regrowth compared to COL and CAZ/AVI. The mean coefficient of determination (R2) for the observed versus predicted bacterial counts was 0.86 (range: 0.75 - 0.95). Bacterial subpopulation susceptibilities and drug mechanistic synergy were essential to describe bacterial killing and growth dynamics. The combination of clinical (hypotension), bacterial (IncR plasmid, aadA2, and sul3) and drug (KC50) variables were most predictive of 30-day mortality. This proof-of-concept study combined clinical, bacterial, and drug variables in a unified model to evaluate clinical outcomes.

Integrating Palliative and Oncology Care for Patients with Advanced Cancer: A Quality Improvement Intervention.

BACKGROUND: Practice guidelines recommend palliative care for patients with advanced cancer, but gaps in access and quality of care persist. OBJECTIVE: To increase goals-of-care (GOC) communication for hospitalized patients with Stage IV cancer. METHODS: An interdisciplinary team designed a quality improvement intervention to enhance oncology palliative care, including training in communication skills and triggers for palliative care consults. SETTING/SUBJECTS: All adult inpatients with Stage IV cancer and unplanned admission at an 804-bed hospital affiliated with a National Cancer Institute (NCI) Comprehensive Cancer Center. MEASUREMENTS: The primary quality measure was the percentage of patients with Stage IV cancer who had a GOC discussion during hospitalization; secondary measures included screening for pain, dyspnea, spiritual needs, and outcomes of intensive care, hospice, and 30-day readmission. RESULTS: In the 11-month study period, n = 330, Stage IV cancer patients were hospitalized. Comparing the first three months with the final three months, rates of GOC discussion increased from 29% to 48% (p = 0.013), and specialty palliative care consultation increased from 18% to 33%, (p = 0.026). Rates of symptom screening, intensive care unit transfer, hospice, and 30-day re-admission did not change overall. However, patients with specialty palliative care more frequently had pain screening (91% vs. 81%, p = 0.020), spiritual assessment (48% vs. 10%, p < 0.001), and hospice referral (39% vs. 9%, p < 0.001), and they were less likely to be re-admitted within 30 days (12% vs. 21%, p = 0.059). DISCUSSION: Interdisciplinary quality improvement was effective to increase GOC discussions and palliative care consults for patients with Stage IV cancer.

Utilization of rapid response resources and outcomes in a comprehensive cancer center*.

OBJECTIVE: To compare the differences in characteristics and outcomes of cancer center patients with other subspecialty medical patients reviewed by rapid response teams. DESIGN: A retrospective cohort study of hospitalized general medicine patients, subspecialty medicine patients, and oncology patients requiring rapid response team activation over a 2-year period from September 2009 to August 2011. PATIENTS: Five hundred fifty-seven subspecialty medical patients required rapid response team intervention. SETTING: A single academic medical center in the southeastern United States (800+ bed) with a dedicated 50-bed inpatient comprehensive cancer care center. INTERVENTIONS: Data abstraction from computerized medical records and a hospital quality improvement rapid response database. MEASUREMENTS AND MAIN RESULTS: Of the 557 patients, 135 were cancer center patients. Cancer center patients had a significantly higher Charlson Comorbidity Score (4.4 vs 2.9, < 0.001). Cancer center patients had a significantly longer hospitalization period prior to rapid response team activation (11.4 vs 6.1 d, p < 0.001). There was no significant difference between proportions of patients requiring ICU transfer between the two groups (odds ratio, 1.2; 95% CI, 0.8-1.8). Cancer center patients had a significantly higher in-hospital mortality compared with the other subspecialty medical patients (33% vs 18%; odds ratio, 2.2; 95% CI, 1.50-3.5). If the rapid response team event required an ICU transfer, this finding was more pronounced (56% vs 23%; odds ratio, 4.0; 95% CI, 2.0-7.8). The utilization of rapid response team resources during the 2-year period studied was also much higher for the oncology patients with 37.34 activations per 1,000 patient discharges compared with 20.86 per 1,000 patient discharges for the general medical patients. CONCLUSIONS: Oncology patients requiring rapid response team activation have a significantly higher in-hospital mortality rate, particularly if the rapid response team requires ICU transfer. Oncology patients also utilize rapid response team resources at a much higher rate.

Acupuncture sensation during ultrasound guided acupuncture needling.

BACKGROUND: Although acupuncture sensation (also known as de qi) is a cornerstone of traditional acupuncture therapy, most research has accepted the traditional method of defining acupuncture sensation only through subjective patient reports rather than on any quantifiable physiological basis. PURPOSE: To preliminarily investigate the frequency of key sensations experienced while needling to specific, quantifiable tissue levels (TLs) guided by ultrasound (US) imaging. METHODS: Five participants received needling at two acupuncture points and two control points at four TLs. US scans were used to determine when each TL was reached. Each volunteer completed 32 sets of modified Southampton Needle Sensation Questionnaires. Part one of the study tested sensations experienced at each TL and part two compared the effect of oscillation alone versus oscillation+rotation. RESULTS: In all volunteers, the frequency of pricking, sharp sensations was significantly greater in shallower TLs than deeper (p=0.007); the frequency of sensations described as deep, dull and heavy, as spreading, and as electric shocks was significantly greater in deeper TLs than shallower (p=0.002). Sensations experienced did not significantly differ between real and control points within each of three TLs (p>0.05) except TL 4 (p=0.006). The introduction of needle rotation significantly increased deep, dull, heavy sensations, but not pricking and sharp sensations; within each level, the spectrum of sensation experienced during both oscillation+rotation and oscillation alone did not significantly differ between acupuncture and control points. CONCLUSION: The preliminary study indicates a strong connection between acupuncture sensation and both tissue depth and needle rotation. Furthermore, the new methodology has been proven feasible. A further study with an objective measurement is warranted.